We have demonstrated that narcotics administered into the spinal subarachnoid space of the rat and rabbit can produce analgesia. The possibility that this route of injection might serve to permit the local application of opiate analgesics for the relief of human pain without the problems of respiratory depression, psychic dependence and the trauma of withdrawal suggested that an extension of these findings to a species closer to man was warranted. Thus, the proposal examines in the rhesus monkey the physiology and pharmacology of this effect. Animals will be implanted with catheters in the spinal subarachnoid space and the effects of intrathecal morphine on the shock titration threshold and thermal escape response examined. In addition, a comprehensive examination of this intrathecal effect on the animal's neurological and vegetative signs will be carried out. The pharmacological specificity of the effect will be examined by testing for stereospecificity, naloxone antagonism at doses approximating the in vivo pA2 of this antagonist and the effects of other opiate agonists. The effects of high doses of intrathecal opiates on tolerance development and the withdrawal sequelia attendent to the injection of systemic naloxone will be studied. To determine where the intrathecal opiates are acting to produce their effect on the nociceptive threshold, the effects of superficially applied morphine on: 1) conduction in the dorsal roots and 2) the activity of spinal nociceptive neurones will be examined. Using radiolabeled morphine, the time course of the behavioral effect and the time course of the effect on neuronal discharge will be correlated with the depth of penetration of the opiate into the dorsal horn. In other experiments, the behavioral characteristics of morphine injected into the periaque-ductal gray and the reticular formation of the primate will be examined in terms of their neurological effects as well as their effects upon the titration and thermal escape measures. The data obtained from the latter paradigm will be analyzed according to the signal detection paradigm in an effort to determine whether the local action of opiates in the several brain regions and in the spinal cord will produce differential effects upon the measures of responses bias and stimulus discriminability. This study thus seeks to define a method which may have significant therapeutic implications as well as extend our theoretical understanding (Text Truncated - Exceeds Capacity)